D(-)-N-(2-methoxy-carbonyl-1-methyl-vinyl)-α-amino-(p-hydroxy-phenyl)-acetic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: D(-)-N-(2-methoxy-carbonyl-1-methyl-vinyl)-α-amino-(p-hydroxy-phenyl)-acetic acid
• 英文别名: 2-(4-hydroxyphenyl)-2-[[(E)-4-methoxy-4-oxobut-2-en-2-yl]amino]acetic acid
• 化学式: C₁₃H₁₅NO₅
• 分子量: 265.266
• InChiKey: VXLHFWHJVCLKPT-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  6

文献信息

• A Novel process for preparation of cefprozil
  申请人：Hetero Drugs Limited

  公开号：EP2213676A1

  公开（公告）日：2010-08-04

  A process for preparing (6R,7R)-7-[2-amino-2-(4-hydroxyphenyl) acetamido]-3-[(Z)-propenyl]-3-cephem-4-carboxylic acid of formula I (cefprozil) or its hydrate, or a pharmaceutically acceptable salt thereof.

  一种制备（6R,7R）-7-[2-氨基-2-(4-羟基苯基)乙酰氨基]-3-[(Z)-丙烯基]-3-头孢烯-4-羧酸（头孢普罗齐尔）或其水合物或其药学上可接受的盐的方法。
• Novel Process For Preparation of Cefprozil Intermediate
  申请人：Parthasaradhi Reddy Bandi

  公开号：US20080281093A1

  公开（公告）日：2008-11-13

  The present invention relates to a process for preparing a key intermediate of cefprozil and use of this intermediate in the preparation of cefprozil thereby avoiding impurity-causing self-acylation. [R-(Z)]-[4-hydroxy-α-[(3-methoxy-1-methyl-3-oxo-1-propenyl)amino]]benzeneacetic acid, mono potassium salt is reacted with ethyl chloroformate to obtain mixed anhydride which is then silylated with N,O-bis(trimethylsilyl)acetamide. The silylated compound obtained is reacted with [7-trimethylsilylamino-3-(Z/E-propen-1-yl)-3-cephem-4-carboxylic acid]trimethylsilyl ester and deprotected with aqueous hydrochloric acid to give cefprozil.

  本发明涉及一种制备头孢普罗酯的关键中间体的方法，以及利用该中间体制备头孢普罗酯，从而避免产生杂质性自酰化。首先将[R-(Z)]-[4-羟基-α-[(3-甲氧基-1-甲基-3-氧代-1-丙烯基)氨基]]苯乙酸单钾盐与氯甲酸乙酯反应得到混合酐，然后用N,O-双(三甲基硅基)乙酰胺进行硅化反应。所得到的硅化合物与[7-三甲基硅氨基-3-(Z/E-丙烯基)-3-头孢烷-4-羧酸]三甲基硅酯进行反应，并用水盐酸去保护，从而得到头孢普罗酯。
• NOVEL PROCESS FOR PREPARATION OF CEFPROZIL INTERMEDIATE
  申请人：PARTHASARADHI REDDY Bandi

  公开号：US20090048460A1

  公开（公告）日：2009-02-19

  The present invention relates to a process for preparing a key intermediate of cefprozil and use of this intermediate in the preparation of cefprozil thereby avoiding impurity-causing self-acylation. [R-(Z)]-[4-hydroxy-α-[(3-methoxy-1-methyl-3-oxo-1-propenyl)amino]] benzeneacetic acid, mono potassium salt is reacted with ethyl chloroformate to obtain mixed anhydride which is then silylated with N,O-bis(trimethylsilyl)acetamide. The silylated compound obtained is reacted with [7-trimethylsilylamino-3-(Z/E-propen-1-yl)-3-cephem-4-carboxylic acid]trimethylsilyl ester and deprotected with aqueous hydrochloric acid to give cefprozil.

  本发明涉及一种制备头孢普罗酯的关键中间体的方法，以及利用该中间体在制备头孢普罗酯过程中避免产生杂质引起的自酰化。首先将[R-(Z)]-[4-羟基-α-[(3-甲氧基-1-甲基-3-酮基-1-丙烯基)氨基]]苯乙酸单钾盐与氯甲酸乙酯反应得到混合酸酐，然后用N，O-双(三甲基硅基)乙酰胺对其进行硅化反应。得到的硅化化合物与[7-三甲基硅氨基-3-(Z/E-丙烯-1-基)-3-头孢烯-4-羧酸]三甲基硅酯发生反应，并用水盐酸去保护，最终得到头孢普罗酯。
• Process for the preparation of 6- D-alpha-amino-(p-hydroxyphenyl)-acetamido penicillanic acid
  申请人：GIST-BROCADES N.V.

  公开号：EP0001133A1

  公开（公告）日：1979-03-21

  Process for the preparation of / D-a-amino-p- hydrox- yphenylacetamido/ groups containing penicillanic acid and cephalosporanic acid derivatives, comprising the acylation of a compounds of the formulae: and/or or and/or wherein R1, R2, and R3 represent the same or a different group and may be selected from a lower alkyl, benzyl, cycloalkyl or phenyl-group and preferably lower alkyl and more preferably a methyl group and wherein X represents a residue selected from the group consisting of hydrogen, acetoxy or a fivemembered heterocyclic thio residue, containing heteroatoms selected from nitrogen, oxygen and/or sulphur and optionally substituted by lower alkyl and wherein an eventually present -NH- radical has optionally been silylated, which compound is previously prepared by the reaction of -6-aminopenicillanic acid or 7-aminocephalosporanic acid or its 3-methyl modifications with at least one equivalent and preferably about 2 with respect to 6-APA, 7-ACA or 7-ADCA and about 3 equivalents with respect to other 3-methyl modifications of 7-ACA of a tri(lower)alkyl silyl groups supplying agent in a dry inert, water insoluble solvent, such as methylene chloride, by rapid mixing of a pre-cooled solution of the compound of formula I-IV with a pre-cooled reaction mixture of at least an equimolar amount of a compound of the formula wherein R4 represents lower alkyl and preferably methyl, R5 represents hydrogen or lower alkyl and preferably methyl, R6 represents lower alkoxy and preferably methoxy and R7 represents lower alkoxy and preferably methoxy, previously prepared from the corresponding Dane salt and an acid chloride under anhydrous conditions in the presence of a tertiary amine as catalyst, such as N-methylmorpholine in a dry, inert, water insoluble, organo solvent such as methylene chloride mixed with a cosolvent or methyl isobutylketone or tetrahydrofuran optionally mixed with a cosolvent, and the continuation of the reactior at a temperature of -10°C or lower and preferably from 2°C to 30°C whereafter the desired compound is recovered by usual methods.

  制备含有青霉素和头孢菌素衍生物的/ D-a-氨基-对羟基-苯基乙酰胺/基团的工艺，包括式中化合物的酰化： 和/或 或 和/或 其中 R1、R2 和 R3 代表相同或不同的基团，可选自低级烷基、苄基、环烷基或苯基，优选低级烷基，更优选甲基，其中 X 代表选自氢、乙酰氧基或五元杂环硫基残基组成的组的残基，五元杂环硫基残基含有选自氮、氧和/或硫的杂原子，可选择被低级烷基取代，其中最终存在的-NH-基可选择被硅烷化、该化合物的制备方法是：将 6-氨基青霉烷酸或 7-氨基头孢烷酸或其 3-甲基修饰物与至少一个当量，就 6-APA、7-ACA 或 7-ADCA 而言最好是约 2 个当量，就 7-ACA 的其他 3-甲基修饰物而言最好是约 3 个当量的三(低级)烷基硅烷基供给剂在干燥的惰性不溶于水的溶剂中反应、将式 I-IV 化合物的预冷溶液与至少等摩尔量的式 I-IV 化合物的预冷反应混合物快速混合，制得三(低级)烷基硅烷基团供给剂的约 3 个当量的 7-ACA 其中 R4 代表低级烷基，最好是甲基；R5 代表氢或低级烷基，最好是甲基；R6 代表低级烷氧基，最好是甲氧基；R7 代表低级烷氧基，最好是甲氧基、在干燥、惰性、不溶于水的有机溶剂如二氯甲烷与助溶剂或甲基异丁基酮或四氢呋喃（任选与助溶剂混合）中，如 N-甲基吗啉，在-10℃或更低温度下，最好在 2℃至 30℃下继续反应，然后用通常的方法回收所需的化合物。
• Process for the preparation of 7-(2-amino-2-phenylacetamido)cephem derivatives and their use for the preparation of antibacterial agents
  申请人：Eisai Co., Ltd.

  公开号：EP0065270A2

  公开（公告）日：1982-11-24

  Improved process for the preparation of 7-(2-amino--2-phenyl-acetamido)cephem derivatives of the general formula (I): wherein R, is a hydrogen atom or hydroxyl group, n stands for 0, 1 or 2, and A denotes a nitrogen-containing heterocyclic group or a direct bond coupling directly the sulfur atom and the -(CH2)nCOOH group together, as well as pharmaceutically acceptable salts thereof. The process is not only simple and easy to carry out, but also provides as crystalline precipitate the intended products with a high yield. The 7-(2-amino-2-phenyl-acetamido)cephem derivatives are useful as intermediates for syntheses of antibacterial agents.

  制备通式(I)的 7-(2-氨基-2-苯基乙酰氨基)头孢衍生物的改进工艺： 其中 R 是氢原子或羟基，n 代表 0、1 或 2，A 表示含氮杂环基团或直接将硫原子和-(CH2)nCOOH 基团耦合在一起的直接键，以及它们的药学上可接受的盐。该工艺不仅简单易行，而且能以高产率提供预期产品的结晶沉淀。7-(2-氨基-2-苯基乙酰氨基)头孢衍生物可作为合成抗菌剂的中间体。